Project summary: An attack or terrorist event using spores of Bacillus anthracis continues to be an imminent threat. In the event of such an attack, many surfaces including human skin will become contaminated with disseminated spores. Spores carried on human skin not only pose the threat of developing into cutaneous anthrax, but can also be carried to other locations distant from the attack site thereby leading to further spore dissemination. This can be particularly problematic if spore contaminated individuals are transported to locations like hospitals where spores shed from the skin may affect debilitated individuals. One important lesson from the events of 2001 is that the infectious dose of anthrax spores may be much lower than originally believed and spores shed from human skin could spread disease far beyond the initial location of an attack. Currently, there is no product specifically designed to decontaminate anthrax spores on human skin. Many of the decontamination regimens under investigation are too harsh for use on skin. Nisin is a peptide antibiotic that is commonly used as a food preservative and has the unique capacity to prevent the germination and outgrowth of bacterial spores. Nisin binds to the surface of the spores and terminates the germination process leaving the spores inert and non-infectious. Nisin is generally recognized as safe and is currently used topically on animals to prevent bacterial infections. We propose to develop nisin-based formulations specifically for neutralization of anthrax spores on human skin. These formulations are intended to be used in addition to antibiotic treatment and vaccination as another layer of defense. This application will select the best formulation of nisin and cofactors to decontaminate anthrax spores using two skin contamination models. We will also study the preventive effects of nisin on two animal models; one which studies germination of spores on wounded skin and one in which pulmonary challenge with spores induces death. [unreadable] [unreadable] Relevance: This application aims to develop a product which is specifically designed to decontaminate anthrax spores on human skin. This product is intended to be used in addition to antibiotics and vaccinations to prevent spread of spores by contaminated skin and anthrax infections of wounds. Currently, no such product exists. [unreadable] [unreadable]